Coeliac Disease

Question 1

Definition

Answer 1

Autoimmune type 4 hypersensitivity reaction to gluten

Question 2

Epidemiology

Answer 2

HLA-DQ2 + 8
Males = Females
Any age (peaks in infancy and 50-60)

Question 3

Risk factors

Answer 3

Family history
Autoimmune:
- Type 1 diabetes
- Autoimmune thyroid disease
- Autoimmune hepatitis
IgA def
Downs syndrome
Turners syndrome

Question 4

Pathophysiology

Answer 4

• Gluten broken down into gliadin in stomach which is a prolamin
• Gliadin is resistant to digestion from protease enzymes (pepsin + chymotrypsin) in SI lumen
• Passes through epithelial wall into cells - into lamina propria
• Deaminated by tissue transglutimase (tTG)
• Taken up by macrophages
• Macrophages present on their surface via MHC II (coded by HLA-DQ2 or 8)
• Activate gluten sensitive CD4 + t cells = produce proinflammatory cytokines
• inflammatory cascade -> TNF + interferon gamma
• Damages villi of SI
• B cells triggered to release anti-tTG + anti-EMA (anti-endomysial antibodies)
• VILLOUS ATROPHY, CRYPT HYPERPLASIA + LYMPHOCYTE INFILTRATION = malabsorpsion

Question 5

Which part of SI affected most

Answer 5

Duodenum + Jejunum affected the most

Question 6

Signs

Answer 6

Malabsorpsion =
- Iron, vitamin B12 or folate def
- Steatorhoea (fatty stinking stools)
- Aphthous ulcers (anaemia)
- Angular stomitis (anaemia)
DERMATITIS HERPETIFORMATIS = IgA skin deposition = itchy vesicular rash
OSTOPENIA = decreased Ca2+ absorption

Question 7

Symptoms

Answer 7

Failure to thrive
Weight loss
Diarrhoea
Fatigue (anaemia)

Question 8

Diagnosis

Answer 8

FIRST LINE = Serum antibody testing
- IgA antibodies against tTG = highly specific and sensitive (may get false negative in IgA def Px)
GOLD STANDARD = Duodenal Biopsy =
- villous atrophy
- crypt hyperplasia
- increase intra-epithelial lymphocytes
- MARSH histological classification used
SECOND LINE = Anti-EMA serology = if anti-tTG weakly positive

Question 9

Management

Answer 9

FIRST LINE = Gluten free diet
- supplements = Iron, B12, folate
Regular DEXA scan to manage osteoporosis
Functional hyposplenism = pneumococcal vaccine. influenza vaccination

Question 10

Complications

Answer 10

Osteoporosis
Malignancy
Infection

Question 11

Differential diagnosis

Answer 11

Tropical sprue = enteropathy associated with tropical travel
- similar on biopsy = CRYPT HYPERPLASIA, VILLOUS ATROPHY
- Tx = often responds well to Abx (e.g tetracycline = DOXYCYCLINE)